"Personalized medicine" is a new clinical paradigm where a specific cancer therapeutic ("smart drug") is prescribed based upon the individual biology of the patient. A goal of personalized medicine is to select individual therapies based upon the correlation of proteomic profiles from diseased tissues with patient response to drug therapy. Therefore, there is a critical need for a practical tool that can generate protein expression profiles from small amounts of tissue samples collected from patients. We hypothesize that cancer patients will be treated more successfully if a correlation between proteomic profiles and drug efficacy is established and that a diagnostic test using our innovative and novel technology, Layered Protein Scanning (LPS), will be able to establish that correlation. The long-term goal of this proposal is to, by the end of Phase II, develop a clinical diagnostic tool that would be used to select and monitor patients most likely to respond to "smart drugs". We will initially focus on clear cell renal carcinoma patients being treated with inhibitors of Epidermal Growth Factor Receptor (EGFr) signaling. To establish proof of principle, in Phase I, we will test the ability of LPS to profile EGFr activity in clear cell renal carcinoma cell lines and tissues. Specifically, we will use LPS to quantitate differences in the levels of total EGFr, activated EGFr, total Erk1/2, activated Erk1/2, total TGF-alpha, and total VHL in: 1) Cell line samples (by comparing LPS-tissue blot with standard western blot) 2) Tissue sections of RCC (by comparing LPS-tissue blot to immunohistochemistry).